Autism and intellectual disability due to a novel gain-of-function mutation in UBE3A.

IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY
Anna M Gunelson, Kwang-Soo Kim, Connolly G Steigerwald, Devorah Segal, Nicolas J Abreu, Jason J Yi
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引用次数: 0

Abstract

The loss of maternal UBE3A causes Angelman syndrome whereas its duplication is associated with a heterogeneous neurodevelopmental disorder. Here, we describe two affected brothers who possess a novel UBE3AL734S variant that is not present in two neurotypical siblings. The UBE3AL734S variant was confirmed to be maternally inherited, and the affected individuals exhibited early global developmental delay, ongoing learning difficulties, and autistic features. Their phenotypes were inconsistent with Angelman syndrome. Biochemical characterization showed the UBE3AL734S variant causes a dramatic increase in the activity of the UBE3A enzyme, suggesting that a gain in UBE3A activity is the driver of neurodevelopmental disease. Our observations document an emerging class of neurodevelopmental disorders caused by gain-of-function mutations in UBE3A.

自闭症和智力残疾是由UBE3A的一种新的功能获得突变引起的。
母体UBE3A的缺失导致Angelman综合征,而其重复则与异质神经发育障碍有关。在这里,我们描述了两个受影响的兄弟,他们拥有一种新的UBE3AL734S变体,这种变体在两个神经正常的兄弟姐妹中不存在。UBE3AL734S变异被证实是母系遗传的,受影响的个体表现出早期的整体发育迟缓、持续的学习困难和自闭症特征。其表型与Angelman综合征不一致。生化表征表明,UBE3AL734S变异引起UBE3A酶活性的急剧增加,这表明UBE3A酶活性的增加是神经发育性疾病的驱动因素。我们的观察记录了一类新兴的由UBE3A的功能获得突变引起的神经发育障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Human Genetics
Journal of Human Genetics 生物-遗传学
CiteScore
7.20
自引率
0.00%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy. Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.
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